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Sensory evaluation combined with high-performance liquid chromatography (HPLC) and amino acid analysis were used to study the effects of withering, rolling, fermentation, and drying (first-drying and sencod-drying) on the main taste substances and their quality formation using one bud and one leaf of Sichuan group species as raw materials. Results showed that the taste intensity profiles of tea samples obtained from different processing procedures differed significantly. During the process of Chuanhong congou black tea, the intensity of sour, salty, and bitter gradually decreased, while the intensity of sweetness gradually increased. The umami intensity increased significantly (P

Abstract Cell division cycle associated 7 (CDCA7) plays a role in various malignancies, especially pancreatic cancer (PC). However, its expression pattern and functional significance in PC require further research. Therefore, this study aimed to investigate CDCA7 expression levels and biological functions in PC using in vitro and in vivo experiments. Western blotting, immunohistochemistry, and real-time polymerase chain reaction were performed to detect CDCA7 expression in PC cells and tissues. Additionally, the biological functions of CDCA7 were assessed using cell proliferation, wound healing, and Transwell assays. CDCA7 overexpression promoted PC cell proliferation, migration, and invasion, and increased resistance to the chemotherapy drug gemcitabine, possibly through enhanced aerobic glycolysis. Additionally, immunoprecipitation assay showed that CDCA7 interacted with STAT3 protein and affected the transcriptional regulation of hexokinase 2. Conclusively, targeting CDCA7 might be a promising therapeutic strategy to increase gemcitabine sensitivity by inhibiting glycolysis in PC cells.

Abstract Recently, there has been growing interest in the role of circular RNAs (circRNAs) in the progression of human cancers. Cellular senescence, a known anti-tumour mechanism, has been observed in several types of cancer. However, the regulatory interplay of circRNAs with cellular senescence in pancreatic cancer (PC) is still unknown. Therefore, we identified circHIF-1α, hsa_circ_0007976, which was downregulated in senescent cells using circRNA microarray analysis. Meanwhile, significantly upregulated expression of circHIF-1α in pancreatic cancer tissue detected by reverse transcription-polymerase chain reaction (RT-qPCR) and in situ hybridization (ISH). High circHIF-1α expression levels were found to independently predict poor survival outcomes. Subsequent treatments with DOX and H2O2 resulted in significantly lower levels of circHIF-1α. CircHIF-1α knockdown induces cellular senescence and suppresses PC proliferation in vitro experiments. The ability of circHIF-1α knockdown to suppress the progression of PC cells was further confirmed in vivo experiments. Our results showed that circHIF-1α is mainly presented in the nucleus of PC cells, also in the cytoplasm. Mechanistically, circHIF-1α inhibited senescence and accelerated the progression of PC cells through miR-375 sponging, thereby promoting HIF-1α expression levels. Nuclear circHIF-1α interacted with human antigen R protein (HUR) to increase HIF-1α expression. Thus, our results demonstrated that circHIF-1α ameliorates senescence and exacerbates growth in PC cells by increasing HIF-1α through targeting miR-375 and HUR, suggesting that targeting circHIF-1α offers a potential therapeutic candidate for PC.

Abstract Pancreatic cancer (PC) is one of the most lethal malignant tumors that lacks effective treatment, and gemcitabine-based chemoresistance occurs frequently. Therefore, new therapeutic strategies for PC are urgently needed. Tripartite motif containing 59 (TRIM59) plays an important role in breast and lung cancer chemoresistance. However, the association between TRIM59 and gemcitabine resistance in PC remains unclear. We identified TRIM59 as an innovative E3 ubiquitin ligase that activated Notch signaling in PC. TRIM59 levels were increased in PC and positively correlated with poor prognosis and gemcitabine resistance in PC patients. TRIM59 facilitated gemcitabine resistance in PC cells in vitro and in vivo. TRIM59 interacted with recombination signal binding protein for immunoglobulin kappa J region (RBPJ) and stabilized it by promoting K63-linked ubiquitination. RBPJ transcriptionally upregulated TRIM59 expression, forming a positive feedback loop with TRIM59. We identified a novel TRIM59 inhibitor, catechin, and confirmed that it sensitized PC cells to gemcitabine. TRIM59 conferred gemcitabine resistance in PC by promoting RBPJ K63-linked ubiquitination, followed by activating Notch signaling. Therefore, our study provides a promising target for gemcitabine sensitization in PC treatment.

Abstract Multispectral pedestrian detection with visible light and infrared images is robust to changes in lighting conditions and therefore is of great importance to numerous applications that require all‐day environmental perception. This paper proposes a novel method named FCE‐RCNN, which integrates saliency detection as a sub‐task and utilizes global information for enhanced feature representation. The approach enhances thermal inputs by incorporating gradients at the raw‐data level before feature extraction. Utilizing a dual‐stream backbone, a global semantic information extraction module is introduced that combines pooling with horizontal–vertical attention mechanisms, capturing high‐quality global semantic information for lower‐level feature enrichment and guidance. Additionally, the pedestrian locality enhancement module is designed to enhance spatial locality information of pedestrians through saliency detection. Furthermore, to alleviate the challenges posed by positional shifts between cross‐spectral features, deformable convolution is innovatively employed. Experimental results on the KAIST dataset demonstrate that FCE‐RCNN significantly improves nighttime detection, achieving a log‐average miss rate of 6.92%, outperforming the new method ICAFusion by 0.93%. These results underscore the effectiveness of FCE‐RCNN, and the method also maintains competitive inference speed, making it suitable for real‐time applications.

Summary: Plasmon-induced transparency is a classical analogue of electromagnetically induced transparency (EIT). However, its realization and control primarily rely on geometry engineering rather than tuning plasmon polaritons (PPs) themselves, due to their relatively poor tunability. Recently discovered polariton modes in low-symmetry materials exhibit volume-confined field distributions, thickness-dependent dispersions, and in-plane anisotropy, offering possibilities for the realization and manipulation of polariton-induced transparency (PIT). In this study, we theoretically achieve geometry-symmetry-free and material-symmetry-guaranteed PIT based on volume-confined phonon polaritons (vPhPs) in stacked bilayer α-MoO3 structures. PIT arises from the strong resonance of vPhPs and the subsequent robust near-field coupling at large thicknesses, where the in-plane anisotropy of vPhPs results in multi-spectral PIT across different polariton bands, enabling the tuning of PIT by adjusting the lattice orientation of α-MoO3 without altering geometry. These findings highlight the potential of polariton modes beyond PPs in PIT systems, with applications in sensors, modulators, and slow light systems.

Abstract Previous studies have shown that the heterogeneity of tumor-associated fibroblasts (CAFs) in the tumor microenvironment may play a critical role in tumorigenesis; however, the biological function of CAFs in pancreatic cancer is still controversial. In this study, we found that CD105-positive (CD105+) CAF-derived exosomes significantly promoted the proliferative and invasive metastatic abilities of pancreatic cancer cells. Furthermore, RNA-seq and qRT‒PCR experiments revealed circAMPK1 as a key molecule in exosomes from CD105+ CAFs that mediates the malignant progression of pancreatic cancer. Furthermore, we demonstrated that circAMPK1 encodes a novel protein (AMPK1-360aa) in pancreatic cancer cells. This protein competes with AMPK1 to bind to the ubiquitination ligase NEDD4, which inhibits AMPK1 protein degradation and ubiquitination and thereby increases AMPK1 levels. Finally, we demonstrated that AMPK1-360aa induces cellular autophagy via NEDD4/AMPK1 to promote the proliferation and invasion of pancreatic cancer cells. In summary, circAMPK1 in CD105+ CAF-derived exosomes may mediate pancreatic cancer cell proliferation and invasive metastasis by inducing autophagy in target cells. Moreover, circAMPK1 may competitively bind to ubiquitinating enzymes through the encoded protein AMPK1-360aa, which in turn inhibits the ubiquitination-mediated degradation of AMPK1 and contributes to the upregulation of AMPK1 expression, thus inducing cellular autophagy to mediate the malignant progression of pancreatic cancer.

The Hutou Beishan Mega Tunnel frequently experiences significant deformation and instability collapse when passing through weak and fractured rock strata, leading to frequent design modifications and adversely impacting the construction progress and costs. This paper employs the finite-discrete element method (FDEM) to investigate the mechanisms and characteristics of large deformations in soft rock and analyzes the effects of in-situ stress and lateral pressure coefficients on the stability of soft rock tunnels. The results indicate that: (1) Once the compressive stress concentration exceeds the shear strength of the surrounding rock, shear failure occurs, with the resulting cracks predominantly forming X-shaped conjugate fractures. The shape of the excavation damage zone (EDZ) corresponds to the stress state; (2) Under hydrostatic stress conditions, the extent of damage to weak surrounding rock is influenced by the in-situ stress. At lower in-situ stress levels, only a few cracks appear at the edges of the surrounding rock, and deformation is minimal. At higher in-situ stress levels, cracks extend deeper into the tunnel, crushing shallow rock; (3) The failure characteristics of the tunnel vary with different lateral pressure coefficients. As the lateral pressure coefficient changes, the shape of the EDZ also changes, and the concentrated damage zone shifts from the arch waist to the crown as the lateral pressure coefficient increases.

Understanding the characteristics of the growth zones of live corals and competitive algae, including turf algae and macroalgae, is crucial for assessing the degradation of coral reef ecosystems. However, identifying live corals and competitive algae in multispectral satellite images is challenging because different objects can have similar spectra. To address this, we used two satellite images acquired at different times (Landsat thematic mapper (TM), Landsat operational land imager (OLI), or Sentinel-2 multi-spectral instrument (MSI)) to assess the growth zone characteristics of live corals and competitive algae. This assessment leveraged the seasonal dieback of competitive algae and the relative stability of live-coral growth zones over a short period. Specifically, we developed a normalized red–green difference index (NRGI) to segment live-coral-or-competitive-alga growth zones in satellite images. By comparing the segmentation results from an image captured during a period with few competitive algae and another image captured during a period with lush competitive algae, we estimated the growth zone areas of the live corals and competitive algae. Finally, we calculated the ratio of the competitive-alga growth zone area to the live-coral growth zone area (RCL). Experiments on eight typical coral islands and reefs in the South China Sea (SCS) from 1995 to 2022 revealed that: (1) the identification accuracies of live-coral-or-competitive-alga growth zones reached 80.3 % and 92.6 % during periods with few competitive algae (January to March) and lush competitive algae (April to October), respectively; (2) the RCL was well correlated with the coral-macroalgae encounter rate (an ecological index indicating the pressure of the competitive algae on the live corals) (r = 0.79, P

In view of the disaster caused by the instability of room-and-pillar goaf, taking the coal pillar left over from a pillar goaf in Yulin as the research background, the roof instability mechanism of room-and-pillar goaf is studied by means of theoretical analysis, physical similarity simulation, numerical analysis and so on. The research results show that the safety factor of the stability of the remaining coal pillar in the mine goaf is 1.54, considering the creep of the coal pillar under the long-term roof load, the large area instability will occur in the end. The influencing factors of the failure and instability of the coal pillar in the room-pillar goaf include five factors, such as physical and mechanical properties of coal, weathering, mining mode, water erosion, creep and so on. The failure law of the catastrophic evolution of roof in room-and-pillar goaf is from point to surface, and the roof from failure to instability is divided into four stages: preliminary failure stage, failure expansion stage, failure aggravation stage and complete instability stage. When the goaf is completely unstable, the peak stress of coal pillar is 15.08 MPa, the stress concentration factor is 3.92, and the roof subsidence displacement is 392.44 mm.

Abstract Post‐translational modification is a rite of passage for cellular functional proteins and ultimately regulate almost all aspects of life. Ubiquitin‐fold modifier 1 (UFM1) system represents a newly identified ubiquitin‐like modification system with indispensable biological functions, and the underlying biological mechanisms remain largely undiscovered. The field has recently experienced a rapid growth of research revealing that UFMylation directly or indirectly regulates multiple immune processes. Here, we summarised important advances that how UFMylation system responds to intrinsic and extrinsic stresses under certain physiological or pathological conditions and safeguards immune homeostasis, providing novel perspectives into the regulatory framework and functions of UFMylation system, and its therapeutic applications in human diseases.

The goal of “carbon peak and carbon neutrality” is China’s responsibility as a major country to maintain global ecological security, and it is also an important way to achieve high-quality development and ecological civilization construction. CO2 emission reduction is imperative.As a result of the energy resource endowment pattern of “rich in coal, poor in oil and less gas”, the main energy in China is still coal with high carbon emission intensity. Coal is an important energy and raw material for high energy-consuming industries such as electric power, iron and steel and coal chemical industry. it plays an important role in the process of achieving the goal of “double carbon”. The coal industry achieves carbon peak through low-carbon transformation, which is the inherent requirement of the high-quality development of coal industry. It is also an important starting point for the implementation of the national “double carbon” strategic goal. Compared with the traditional natural mineralization raw materials, coal-based solid waste mineralization and storage CO2 has the advantages of rich raw materials, friendly products, low energy consumption and rapid reaction. At the same time, it can produce high value-added products for chemical industry, construction and other fields. The characteristics of main coal-based solid waste coal gangue, fly ash, desulphurization gypsum, gasification slag and furnace bottom slag in China are introduced, the main CO2 emission sources and production in China are analyzed, and the in-situ and ex-situ CO2 mineralization technologies according to different mineralization and storage locations and direct and indirect carbonation technologies according to mineralization mechanism are reviewed. The research progress of CO2 mineralization and storage technology using coal-based solid waste as raw material is reviewed, and it is found that this technology has harsh reaction conditions, high cost, small treatment scale, and the research is still in the laboratory stage. This paper briefly describes the mineralization and storage technology of CO2 with coal-based solid waste as carrier and goaf as storage source, which mainly includes two technologies: construction of functional filling body and preparation of negative carbon filling material. The existing problems and future research direction of coal-based solid waste mineralization and storage of CO2 are analyzed. For the CO2 mineralization technology with coal-based solid waste as raw material, the technological process should be optimized, the reaction cost should be reduced, and the research on industrialization promotion should be further strengthened. aiming at the CO2 mineralization and storage technology with coal-based solid waste as carrier and goaf as storage source, the research on deep mineralization mechanism, storage risk assessment and long-term stability should be strengthened in the future, so as to improve the storage scale and long-term stability of CO2. On this basis, the slurry filling material is prepared from coal-based solid waste, with water as carrier, pump as power and pipeline as channel, the filling material and CO2 are transported to the goaf for mineralization reaction, and combined with microbial induced calcium carbonate precipitation (MICP) technology, the mining fissures in rock mass are closed to realize CO2 mineralization and storage.

With the rapid growth of the electric vehicle industry, the demand for battery fault detection methods is also growing. Effective battery defect detection methods help maintain the performance of the battery pack. In this research, a reconstruction-based model for internal short circuit (ISC) detection in battery packs is presented by combining transformer and long short-term memory (LSTM). LSTM is added to the model to improve the encoding results of the transformer. The optimized decoders have a positive effect on the fitting ability of the model. In this model, the voltage data of the battery packs are taken as input and residual signals are generated by the differences between the reconstructed and true values to detect the ISC. The online parameter update method is proposed to increase the ability of the neural network model to screen out fault signals more efficiently, and the false-positive clipping method is employed to enhance detection accuracy. A large amount of data, including ISC, was collected from the laboratory to test the sensitivity and robustness. The verification results show that our model has better fitting ability and sensitivity. The parameter update method and false-positive clipping method help improve the adaptability and robustness. Our detection method achieves 96.05%, 98.57%, and 96.40% accuracy in ISC detection of 1 ohm, 5 ohms, and 10 ohms respectively.

Accurate estimating the state of health (SOH) of lithium-ion battery plays a significant role in the safe operation of electric vehicles. With the development of deep learning, neural network-based methods have attracted much attention from researchers. While most of the existing SOH estimation methods are built by a single network, failing to sufficiently extract data information, and thus leading to the limited accuracy and generality (i.e., such a single network makes it difficult to estimate the SOH of battery, with different types and working conditions). Towards this issue, a novel hybrid network, called HFCM (Hierarchical Feature Coupled Module)-LSTM (Long–short-term memory), is designed to fully extract the original data information, making it more accurate to estimate the SOH of battery, with different types and working conditions. Specifically, the proposed HFCM-LSTM mainly consists of two components, HCFM and LSTM. The HCFM is proposed to comprehensively extract the original data feature information from the original samples. On the other hand, following the HFCM, a LSTM module is employed to model time series information. Based on this HFCM-LSTM network, the data obtained directly from the battery are fed into the model as input, enabling an end-to-end SOH estimation of the battery. A series of experiments are conducted on both NASA dataset and Oxford dataset, the experimental results demonstrate that the proposed SOH estimation algorithm outperforms several existing state-of-the-art methods, in terms of accuracy and generality.

The downward shortwave radiation (DSR) is a key input parameter for land surface models and climate models. Based on the daily averaged Global Land Surface Satellite downward shortwave radiation (GLASS-DSR) dataset over the Yunnan-Kweichow Plateau (YKP) from 1984 to 2018, this paper analyzes variation trend and breakpoints of DSR. The results show that: annual averaged DSR decreases at a decreasing rate of −1.84 W·m−2·decade−1 over the YKP from 1984 to 2018; the overall distribution of interannual averaged DSR shows higher in the mid-west, and gradually decreasing from west to northeast over the YKP; the estimated averaged DSR is larger in spring than in summer due to the influence of the monsoon; monthly averaged DSR reaches its maximum in May and its minimum in December; breakpoints are found in the seasonal and trend components of daily averaged DSR. Eleven driving factors are examined for their effects on DSR variation, including annual average temperature, precipitation, 10 m wind speed, aerosol optical thickness (AOT), total cloud cover, elevation, slope, aspect, longitude, latitude, and climate zones. According to the findings, AOT predominates in the spatio-temporal distribution of DSR over the YKP. This study will contribute to studies related to climate change and highland radiation.

Abstract Pancreatic cancer (PC), a gastrointestinal tract malignant tumor, has a poor prognosis due to early metastasis and limited response to chemotherapy. Therefore, identifying novel therapeutic approaches for PC is critical. Epithelial–mesenchymal transition (EMT) is known as the vital progress in PC development, we constructed the EMT-related prognosis model to screen out that FOXQ1 probably involving in the EMT regulation. FOXQ1 has been linked to the malignant process in a number of cancers. However, its function in PC is unknown. In our work, the expression of FOXQ1 was elevated in PC tissues, and a high level of FOXQ1 in PC was linked to patients’ poor prognosis. FOXQ1 overexpression promoted aerobic glycolysis and enhanced PC cell proliferation, tumor stemness, invasion, and metastasis. Whereas, FOXQ1 silencing showed the reverse effect. Furthermore, mechanistic studies indicated that FOXQ1 promotes LDHA transcription, and thus modulates aerobic glycolysis to enhance PC cell proliferation, tumor stemness, invasion, and metastasis by increasing LDHA expression. Therefore, these novel data suggest that FOXQ1 may be a possible therapeutic target in PC.

Abstract Background Studies reporting the effects of metabolic surgery, lifestyle intervention, and intensive insulin therapy for the remission of type 2 diabetes (T2DM) has been increasing, with fruitful results better conducted and yielded. However, there are only a few studies on the remission of T2DM using oral hypoglycemic drugs. Therefore, this study aims to investigate the remission effect of canagliflozin and metformin on participants with newly diagnosed T2DM and its possible underlying mechanism(s) through which these two medications elicit diabetes remission. Method To this end, we performed a multicenter, parallel-group, randomized, controlled, and open-label trial. A total of 184 participants with a ≤ 3-year course of T2DM will be enrolled and randomly assigned to the canagliflozin or metformin treatment group in a ratio of 1:1. Participants in each group will maintain their medication for 3 months after achieving the target blood glucose level and then stop it. These participants will be followed up for one year to determine remission rates in both groups. Discussion In this study, we will establish that whether canagliflozin is superior to metformin in terms of remission rate in participants with newly diagnosed T2DM. The results of this trial may provide robust evidence regarding the efficacy and mechanisms of the action of sodium-glucose cotransporter-2 inhibitors (SGLT2is) in T2DM remission. Trial registration ChiCTR2100043770(February 28, 2021).

BackgroundThis study aimed to investigate the effect of different doses of dexmedetomidine combined with sufentanil on postoperative analgesia in developmental hip dislocation in children after Salter osteotomy.MethodsThe clinical data of 98 children with developmental hip dislocation, who underwent Salter osteotomy in our center between January 2020 and February 2023, were selected. The children were randomly divided into four groups based on the application of patient-controlled intravenous analgesia (sufentanil + granisetron ± dexmedetomidine). All children received 1 µg/kg/day of sufentanil and 3 mg of granisetron. Group A did not receive dexmedetomidine, and Groups B, C, and D received 0.5, 0.75, and 1.0 µg/kg/day of dexmedetomidine, respectively. The pain indicators and immune factor levels of children in each group were compared.ResultsThe heart rate (HR) and respiratory rate (RR) 2 h after operation in Groups C and D were significantly lower than those in Groups A and B (P

Bone defects induced by trauma, infection, and tumors present a significant challenge for treatment in clinical trials. Biomaterial-based tissue engineering strategy has shown great promise in bone defect repair. However, multiple functions inherent in the extracellular matrix (ECM) are rarely covered in the design of scaffold materials associated with bone grafting procedures. These deficiencies significantly limit its potential application in pathologic bone defect therapy. In this work, we constructed a hydrogel scaffold mimicking the dynamic features of ECM with the combination of antimicrobial and osteogenic capabilities as well, to investigate its applications in the therapy of infected radial defects. The hydrogel scaffold enables not only minimally invasive implantation but also adaptability and adhesion to irregular defect shapes. Both in vitro and in vivo assays have indicated that the hydrogel scaffold could rapidly eradicate bacteria, restore the infection-induced localized inflammatory microenvironment. Further loading osteogenic growth peptide (OGP) to recruit stem cells promotes osteogenic differentiation and ultimately enhances bone regeneration in the defect region. In summary, our work indicated that hydrogels with ECM-related inherent bioactivities and dynamic inner structures represent a feasible solution as a tissue bionic substitute for the therapy of infected bone defects.

Abstract Background Gemcitabine resistance (GR) is a significant clinical challenge in pancreatic adenocarcinoma (PAAD) treatment. Macrophages in the tumor immune-microenvironment are closely related to GR. Uncovering the macrophage-induced GR mechanism could help devise a novel strategy to improve gemcitabine treatment outcomes in PAAD. Therefore, preclinical models accurately replicating patient tumor properties are essential for cancer research and drug development. Patient-derived organoids (PDOs) represent a promising in vitro model for investigating tumor targets, accelerating drug development, and enabling personalized treatment strategies to improve patient outcomes. Methods To investigate the effects of macrophage stimulation on GR, co-cultures were set up using PDOs from three PAAD patients with macrophages. To identify signaling factors between macrophages and pancreatic cancer cells (PCCs), a 97-target cytokine array and the TCGA-GTEx database were utilized. The analysis revealed CCL5 and AREG as potential candidates. The role of CCL5 in inducing GR was further investigated using clinical data and tumor sections obtained from 48 PAAD patients over three years, inhibitors, and short hairpin RNA (shRNA). Furthermore, single-cell sequencing data from the GEO database were analyzed to explore the crosstalk between PCCs and macrophages. To overcome GR, inhibitors targeting the macrophage-CCL5-Sp1-AREG feedback loop were evaluated in cell lines, PDOs, and orthotopic mouse models of pancreatic carcinoma. Results The macrophage-CCL5-Sp1-AREG feedback loop between macrophages and PCCs is responsible for GR. Macrophage-derived CCL5 activates the CCR5/AKT/Sp1/CD44 axis to confer stemness and chemoresistance to PCCs. PCC-derived AREG promotes CCL5 secretion in macrophages through the Hippo-YAP pathway. By targeting the feedback loop, mithramycin improves the outcome of gemcitabine treatment in PAAD. The results from the PDO model were corroborated with cell lines, mouse models, and clinical data. Conclusions Our study highlights that the PDO model is a superior choice for preclinical research and precision medicine. The macrophage-CCL5-Sp1-AREG feedback loop confers stemness to PCCs to facilitate gemcitabine resistance by activating the CCR5/AKT/SP1/CD44 pathway. The combination of gemcitabine and mithramycin shows potential as a therapeutic strategy for treating PAAD in cell lines, PDOs, and mouse models.

Abstract Context Naru 3 pill is a traditional Mongolian medicine for the treatment of intervertebral disc degeneration (IDD), but the mechanism is not yet clear. Objective This study investigated the mechanism of Naru 3 pill in the treatment of IDD. Materials and methods Active ingredients and related targets of Naru 3 pill, as well as IDD-related genes, were collected from public databases. The analysis was performed by protein‒protein interaction network analysis, gene ontology and Kyoto Gene and Genome Encyclopedia (KEGG) functional enrichment analysis, molecular docking and molecular dynamics simulations. Finally, the network pharmacology results were validated by in vitro experiments. Results Network analysis showed that sesamin, piperine and ellagic acid were potential key components and CASP3, BAX and BCL2 were key targets. KEGG analysis indicated the apoptotic pathway as a potential pathway. Molecular docking showed that sesamin interacted better with the targets than the other components. The results of molecular dynamics simulations indicated that the three systems BAX-sesamin, BCL2-sesamin and CASP3-sesamin were stable and reasonable during the simulation. In vitro experiments showed that sesamin had the least effect on cell growth and the most pronounced proliferation-promoting effect, and so sesamin was considered the key component. The experiments confirmed that sesamin had antiapoptotic effects and reversed the expression of CASP3, BAX and BCL2 in degeneration models, which was consistent with the network pharmacology results. Furthermore, sesamin alleviated extracellular matrix (ECM) degeneration and promoted cell proliferation in the IDD model. Conclusion The present study suggested that Naru 3 pill might exert its therapeutic and antiapoptotic effects on IDD by delaying ECM degradation and promoting cell proliferation, which provides a new strategy for the treatment of IDD.

Background: Diallyl trisulfide (DATS), a compound derived from garlic, has been demonstrated its anti-cancer properties. While it has been shown to inhibit the expression of epidermal growth factor receptor (EGFR) in various cancers, its effects on osteosarcoma (OS) cells remain unclear. This study aimed to investigate the impacts of DATS on OS cells growth, migration, invasion, epithelial-mesenchymal transition (EMT) and autophagy, as well as its underlying mechanisms which was involving in the EGFR/PI3K/AKT/mTOR pathway. Methods: In this study, human osteosarcoma cells (143B) were treated with different concentrations of DATS (10, 50, 100 and 200 μM) for 24 and 48 h, respectively. Cell viability was measured using CCK8, the half lethal concentration was selected for the following experiments. Wound healing and transwell assays were performed to evaluate migration and invasion abilities, while flow cytometry was used to measure apoptosis. Quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blotting, and confocal imaging were employed to analyze the related mRNA and protein expression levels of epithelial-mesenchymal transition (EMT), EGFR/Phosphoinositide 3 kinase (PI3K)/AKT/Mammalian target of rapamycin (mTOR) signaling pathway and autophagy-related markers. Results: DATS significantly inhibited proliferation, migration and EMT in osteosarcoma cells. Additionally, DATS promoted cell apoptosis and induced autophagy, which could be rescued by the autophagy inhibitor 3-methyladenine (3-MA). Moreover, DATS treatment led to the inactivation of the EGFR/PI3K/AKT/mTOR pathway in osteosarcoma cells. Conclusions: This study demonstrated that DATS inhibited osteosarcoma cell growth, migration and EMT, but inducing apoptosis and autophagy. These effects were mediated by the inactivation of the EGFR/PI3K/AKT/mTOR signaling pathway. These findings suggested that DATS could serve as a potential therapeutic agent for osteosarcoma treatment.

Abstract Modern Fe‐Si oxyhydroxide deposits occur in global marine hydrothermal vent sites. Despite their role as biogenic substrates and potential ore resources, much remains unknown about their formation processes. Here, we apply analyses of major and trace elements as well as Sr‐Nd‐Pb‐Fe isotopes combined with 238U‐230Th dating to Fe‐Si oxyhydroxides obtained from several hydrothermal fields along the Southwest Indian Ridge. These mineralized oxyhydroxides primarily consist of poorly crystalline two‐line ferrihydrite and amorphous opal‐A, with lesser amounts of nontronite and birnessite. The ubiquitous and characteristic Fe‐rich ultrastructures in the oxyhydroxides directly indicate microbial activity. The 238U‐230Th dating constrains their crystallization ages from ca. 11,873 to 384 years old. The seawater‐like 87Sr/86Sr and varying 143Nd/144Nd ratios underline a high proportion of seawater mixed with hydrothermal fluids. The radiogenic Pb isotopic patterns suggest a primary derivation of Pb leached from substrate basalts and to a lesser extent Pb from seawater. Stable iron isotopic compositions for different oxyhydroxides display a remarkable range between −1.47 and 0.82‰, which were interpreted as reflecting the fractionation processes during the formation of the deposits under evolving depositional redox conditions. The partial oxidation of Fe(II) and the subsurface removal of isotopically heavy Fe oxyhydroxides are suggested to play a vital role in shifting the Fe isotopic signature toward more negative values. Given that these Fe‐Si oxyhydroxide deposits exhibit features similar to certain ancient iron formations (IFs), Fe isotope systematics of these deposits may hold significant potential for fingerprinting the biological Fe oxidation processes that drove IF deposition on early Earth.

The processing damages such as delamination and tearing were easily produced during the drilling of the sleeve holes of GFRP, which were directly related to the axial drilling force. In order to improve the quality of GFRP hole-making, a new diamond thin-wall trepanning tool was adopted; and combined with the low-frequency axial vibration machining technology, the kinematic model and the dynamic model of single abrasive particle were established. The variation law of axial force in GFRP hole-making was experimentally studied. The burning probability and the automatic blanking rate of trepanning tool were analyzed. The results show that the instantaneous feed rate and the axial force of low-frequency vibration drilling are larger than that of conventional drilling. Besides, the axial force increases with the increase of amplitude, and the axial forces of the low-frequency vibration drilling and the conventional drilling increase with the increase of feed speed and decrease with the increase of spindle speed. At the same time, the abrasive particles participate in drilling intermittently, which greatly reduces the burning probability of the trepanning drill and improves its automatic blanking rate. The automatic blanking rate during low-frequency vibration drilling is up to 88.24%, which can realize the continuous batch hole-making of GFRP.

Multi-vehicle tracking is one of the most crucial components of an intelligent transportation system (ITS). However, when it comes to busy traffic flow, tracking targets robustly becomes more problematic due to occlusion, motion blur, high appearance similarity, etc. To achieve accurate and efficient tracking performance, we present a novel multi-vehicle tracking method based on the enhanced detection model and joint scoring strategy. Specifically, the former aims to (1) adopt lightweight yet efficient YOLOv5s to improve detection accuracy and running speed, and (2) incorporate the CBAM and transformer encoder modules into the detection model to generate the refined features for the target localization. The Latter preferentially provides high-confidence detections and tracklets for subsequent data association, significantly reducing the number of identity switches and redundant vehicle trajectories caused by mutual occlusion, similar object interference, etc. We evaluated the proposed multivehicle tracking approach on the UA-DETRAC vehicle tracking dataset and demonstrated its superior capabilities through intensive comparison and analysis. Moreover, our proposed method runs at 24.4 FPS on a single GPU and meets the real-time requirement.

Background TMUB1 is a transmembrane protein involved in biological signaling and plays an important role in the stability and transcription of P53. However, its role in tumor remains unknown. Methods Using R language, the expression level of 33 cancer spectrum TMUB1 was analyzed by the public database TCGA, GEO and HPA, the differential expressed gene (DEG) screening and protein interaction (PPI) network was constructed, and the differential genes of TMUB1 in colon cancer were identified. The relevant signaling pathways were identified by gene functional annotation and enrichment analysis. The ssGSEA algorithm in GSVA were used for immune infiltration analysis. The Kaplan-Meier analysis, univariate and multivariate Cox regression analysis, nomogram and calibration map analysis were constructed to evaluate the correlation between TMUB1 expression and clinical prognosis. The expression levels of TMUB1 in intestinal cancer cell lines as well as in 10 intestinal cancer tissues were verified by qPCR experiments. Results Through the bioinformatics analysis of multiple databases and preliminary experimental studies, we found that the expression of TMUB1 was significantly increased in colon cancer tumors, and was correlated with the clinical N stage, pathological grade, lymphatic metastasis and BMI of colon cancer. TMUB1 may be involved in the regulation of the malignant progression of colon cancer. Meanwhile, patients with high expression of TMUB1 mRNA had worse OS and DSS, and TMUB1 expression was an independent prognostic factor for OS and DSS. It was further found that highly expressed TMUB1 tissues showed low levels of immune infiltration and stromal infiltration. Conclusion We reported the expression level of TMUB1 in colon cancer and analyzed its potential prognostic value in colon cancer through the bioinformatics analysis and preliminary experimental studies. The high expression of TMUB1 is a negative prognostic factor for colon cancer patients. TMUB1 may be a potential target for colon cancer.

Tremendous amounts of materials and energy are transported from the East China Sea (ECS) to the East/Japan Sea (EJS) through the Korea/Tsushima Strait (KTS). Tides undoubtedly play an important role in regulating ocean circulation on the broad continental shelf of the ECS, while the effects of tides on the water exchange between the ECS and EJS remain unclear. Using a three-dimensional Regional Oceanic Modeling System (ROMS) circulation model, we conducted numerical experiments with tides, without tides, and only barotropic tides. The results showed that the water flux across the KTS can increase by up to 13% (in summer) when excluding tides from the numerical simulation. To understand how tidal forcing regulates the KTS water flux, we performed a dynamic diagnostic analysis and revealed that the variation in sea surface height under tidal effect is the main reason for the water flux variation across the KTS. The tidal effect can adjust the sea surface height, weaken the pressure gradient and reduce the water flux across the KTS, which affect the intensity of water exchange between the ECS and EJS. The tidal effect can alter sea level difference between the Taiwan Strait and the KTS, which influences the KTS water flux. Tides can also influence the KTS water flux by altering the sea surface height through interaction with topography and stratification. We also found that tidal effect weakens the northward intrusion of the Yellow Sea Warm Current in winter and in turn enhances the water flux across the KTS according to volume conservation. These modeling results imply that tides must be considered when simulating the ocean environment of the northwestern Pacific Ocean.

BackgroundResearch on diabetes remission has garnered prominence in recent years. However, to date, no pertinent bibliometric study has been published. This study sought to elucidate the current landscape and pinpoint potential new research directions through a bibliometric analysis of diabetes remission.MethodsWe perused relevant articles on diabetes remission from January 1, 2000, to April 16, 2023, in the Web of Science. We utilized CiteSpace software and VOSviewer software to construct knowledge maps and undertake analysis of countries, institutional affiliations, author contributions, journals, and keywords. This analysis facilitated the identification of current research foci and forecasting future trends.ResultsA total of 970 English articles were procured, and the annual publication volume manifested a steady growth trend. Most of the articles originated from America (n=342, 35.26%), succeeded by China and England. Pertaining to institutions, the University of Newcastle in England proliferated the most articles (n=36, 3.71%). Taylor R authored the most articles (n=35, 3.61%), and his articles were also the most co-cited (n=1756 times). Obesity Surgery dominated in terms of published articles (n=81, 8.35%). “Bariatric surgery” was the most prevalently used keyword. The keyword-clustering map revealed that the research predominantly centered on diabetes remission, type 1 diabetes, bariatric surgery, and lifestyle interventions. The keyword emergence and keyword time-zone maps depicted hotspots and shifts in the domain of diabetes remission. Initially, the hotspots were primarily fundamental experiments probing the feasibilities and mechanisms of diabetes remission, such as transplantation. Over the course, the research trajectory transitioned from basic to clinical concerning diabetes remission through bariatric surgery, lifestyle interventions, and alternative strategies.ConclusionOver the preceding 20 years, the domain of diabetes remission has flourished globally. Bariatric surgery and lifestyle interventions bestow unique advantages for diabetes remission. Via the maps, the developmental milieu, research foci, and avant-garde trends in this domain are cogently portrayed, offering guidance for scholars.

Atherosclerosis is an important cause of cerebrovascular and cardiovascular disease (CVD). Lipid infiltration, inflammation, and altered vascular stress are the critical mechanisms that cause atherosclerotic plaque formation. The hallmarks of the progression of atherosclerosis include plaque ulceration, rupture, neovascularization, and intraplaque hemorrhage, all of which are closely associated with the occurrence of CVD. Assessing the severity of atherosclerosis and plaque vulnerability is crucial for the prevention and treatment of CVD. Integrating imaging techniques for evaluating the characteristics of atherosclerotic plaques with computer simulations yields insights into plaque inflammation levels, spatial morphology, and intravascular stress distribution, resulting in a more realistic and accurate estimation of plaque state. Here, we review the characteristics and advancing techniques used to analyze intracranial and extracranial atherosclerotic plaques to provide a comprehensive understanding of atheroma.

Abstract Background Sodium formononetin-3ʹ-sulphonate (Sul-F) may alleviate I/R injury in vivo with uncertain mechanism. Endoplasmic reticulum (ER) stress-mediated apoptosis participates in the process of cerebral ischemia‐reperfusion (I/R) injury. Our aim is to figure out the effect of Sul-F on cerebral I/R injury and to verify whether it works through suppressing ER stress-mediated apoptosis. Results The cerebral lesions of middle cerebral artery occlusion (MCAO) model in SD rats were aggravated after 24 h of reperfusion, including impaired neurological function, increased infarct volume, intensified inflammatory response and poor cell morphology. After intervention, the edaravone (EDA, 3 mg/kg) group and Sul-F high-dose (Sul-F-H, 80 mg/kg) group significantly alleviated I/R injury via decreasing neurological score, infarct volume and the serum levels of inflammatory factors (TNF-α, IL-1β and IL-6), as well as alleviating pathological injury. Furthermore, the ER stress level and apoptosis rate were elevated in the ischemic penumbra of MCAO group, and were significantly blocked by EDA and Sul-F-H. In addition, EDA and Sul-F-H significantly down-regulated the ER stress related PERK/eIF2α/ATF4 and IRE1 signal pathways, which led to reduced cell apoptosis rate compared with the MCAO group. Furthermore, there was no difference between the EDA and Sul-F-H group in terms of therapeutic effect on cerebral I/R injury, indicating a therapeutic potential of Sul-F for ischemic stroke. Conclusions Sul-F-H can significantly protects against cerebral I/R injury through inhibiting ER stress-mediated apoptosis in the ischemic penumbra, which might be a novel therapeutic target for ischemic stroke.

Abstract Morphogenesis and organogenesis in the low organisms have been found to be modulated by a number of proteins, and one of such factor, deformed epidermal auto-regulatory factor-1 (DEAF-1) has been initially identified in Drosophila. The mammalian homologue of DEAF-1 and structurally related proteins have been identified, and they formed a family with over 20 members. The factors regulate gene expression through association with co-repressors, recognition of genomic marker, to exert histone modification by catalyze addition of some chemical groups to certain amino acid residues on histone and non-histone proteins, and degradation host proteins, so as to regulate cell cycle progression and execution of cell death. The formation of fused genes during chromosomal translocation, exemplified with myeloid transforming gene on chromosome 8 (MTG8)/eight-to-twenty one translocation (ETO) /ZMYND2, MTG receptor 1 (MTGR1)/ZMYND3, MTG on chromosome 16/MTGR2/ZMYND4 and BS69/ZMYND11 contributes to malignant transformation. Other anomaly like copy number variation (CNV) of BS69/ZMYND11 and promoter hyper methylation of BLU/ZMYND10 has been noted in malignancies. It has been reported that when fusing with Runt-related transcription factor 1 (RUNX1), the binding of MTG8/ZMYND2 with co-repressors is disturbed, and silencing of BLU/ZMYND10 abrogates its ability to inhibition of cell cycle and promotion of apoptotic death. Further characterization of the implication of ZMYND proteins in carcinogenesis would enhance understanding of the mechanisms of occurrence and early diagnosis of tumors, and effective antitumor efficacy.

Abstract Pancreatic cancer (PC) is one of the most malignant types of cancer, and is characterized by early metastasis, limited response to chemotherapeutics, and poor prognosis. Therefore, there is an urgent need to explore new therapeutic strategies for PC treatment. Human rhomboid-like 2 (RHBDL2) is differentially expressed in cervical and breast cancer. However, the correlation between RHBDL2 and PC remains unclear. We found that RHBDL2 is highly expressed in human PC cells and tissues and is significantly associated with distant metastasis and poor survival of patients with PC. Gain- and loss-of-function assays indicated that RHBDL2 could accelerate PC cell proliferation and mobility in vitro and in vivo. The RNA-Seq results suggest that RHBDL2 may be involved in the activation of Notch signaling pathway. IMR-1 could restore the proliferation and metastatic capacity of PC cells mediated by RHBDL2. RHBDL2 interacted with and cleaved Notch1, resulting in the release of N1ICD. RHBDL2 decreased the ubiquitination level of N1ICD and collaborated with Ovarian tumor domain-containing 7B (OTUD7B) to stabilize N1ICD via the ubiquitin-proteasome pathway. RHBDL2 facilitated PC cell proliferation and mobility by stabilizing the N1ICD via the OTUD7B and activating the Notch signaling pathway. Thus, targeting this novel pathway may be a potential therapeutic strategy for PC.

Abstract Background MICAL1 is involved in the malignant processes of several types of cancer; however, the role of MICAL1 in pancreatic cancer (PC) has not been well-characterized. This study aimed to investigate the expression and function of MICAL1 in PC. Methods RT-qPCR and immunohistochemistry were used to detect MICAL1 expression in PC and adjacent nontumor tissues. Cell Counting Kit-8, EdU, clone formation, wound healing, and Transwell assays as well as animal models were used to investigate the effects of overexpression or inhibition of MICAL1 expression on the proliferation, invasion, and metastasis of PC cells. RNA-seq was used to explore the main pathway underlying the functions of MICAL1. Proteomics, mass spectrometry, and co-immunoprecipitation assays were used to investigate the interaction of proteins with MICAL1. Rescue experiments were conducted to validate these findings. Results Both MICAL1 mRNA and protein levels were upregulated in PC tissues compared with matched adjacent nontumor tissues. The expression level of MICAL1 was associated with the proliferative and metastatic status of PC. Repression of MICAL1 significantly inhibited PC cell growth, migration, and invasion in vitro and in vivo. RNA sequencing analysis indicated that MICAL1 was closely correlated with the WNT pathway. Overexpression of MICAL1 (1) promoted the phosphorylation of TBC1D1 at the Ser660 site, (2) facilitated the distribution of FZD7 on the cytomembrane, (3) inhibited the degradation of FZD7 in the lysosome, and (4) activated the WNT pathway. Conclusions MICAL1 was upregulated in PC and involved in stimulating the progression of PC cells by activating the WNT/β-catenin signaling pathway. Therefore, MICAL1 is a potential therapeutic target for PC.

Abstract Pancreatic cancer (PC) is prone to distant metastasis in the early stage, which is attributed to the strong migration ability of tumor cells. Focal adhesion turnover is essential for cancer cell metastasis, and the integrin recycling process is a key activation pathway for focal adhesion depolymerization. To identify the key motor protein involving in the integrin β1 recycling, we screened kinesin proteins involved in integrin β1 recycling using a kinesin family siRNA library and identified kinesin family 15 (KIF15) as a key regulator. KIF15 was upregulated in metastasis PC tissues and promoted PC cell migration and invasion. We identified KIF15 as a key component mediating integrin β1/FAK signaling that accelerated FA disassembly in a FAK-Y397-dependent manner. KIF15 recruited PI3K-C2α to promote integrin β1/FAK signaling and FA disassembly in a RAB11A-dependent manner. The C-terminal tail of KIF15 is required for the PI3K-C2α interaction and RAB11A activation. In addition, we also found that SIRT1-mediated acetylation of KIF15 is essential for KIF15 phosphorylation, which is the key activation event in motor protein function. Together, these findings indicate that KIF15 interacts with PI3K-C2α to promote FA turnover in PC cells by controlling the endosome recycling of integrin β1 in a SIRT1 acetylation modification-dependent manner, eventually promoting focal adhesions turnover and distant metastasis in PC.

Adipokines are biologically active factors secreted by adipose tissue that act on local and distant tissues through autocrine, paracrine, and endocrine mechanisms. However, adipokines are believed to be involved in an increased risk of atherosclerosis. Classical adipokines include leptin, adiponectin, and ceramide, while newly identified adipokines include visceral adipose tissue-derived serpin, omentin, and asprosin. New evidence suggests that adipokines can play an essential role in atherosclerosis progression and regression. Here, we summarize the complex roles of various adipokines in atherosclerosis lesions. Representative protective adipokines include adiponectin and neuregulin 4; deteriorating adipokines include leptin, resistin, thrombospondin-1, and C1q/tumor necrosis factor-related protein 5; and adipokines with dual protective and deteriorating effects include C1q/tumor necrosis factor-related protein 1 and C1q/tumor necrosis factor-related protein 3; and adipose tissue-derived bioactive materials include sphingosine-1-phosphate, ceramide, and adipose tissue-derived exosomes. However, the role of a newly discovered adipokine, asprosin, in atherosclerosis remains unclear. This article reviews progress in the research on the effects of adipokines in atherosclerosis and how they may be regulated to halt its progression.

Abstract Although FOXD1 has been found to be involved in the malignant processes of several types of cancers, its role in pancreatic cancer (PC) is not well understood. This study aimed to investigate the expression and function of FOXD1 in PC. We found that FOXD1 mRNA and protein expression were upregulated in PC tissues compared with non-tumor tissues, and high expression level of FOXD1 was associated with an adverse prognostic index of PC. The results of in vitro and in vivo assays indicate that overexpression of FOXD1 promotes aerobic glycolysis and the capacity of PC cells to proliferate, invade, and metastasize, whereas FOXD1 knockdown inhibits these functions. The results of mechanistic experiments suggest that FOXD1 can not only directly promote SLC2A1 transcription but also inhibit the degradation of SLC2A1 through the RNA-induced silencing complex. As a result, FOXD1 enhances GLUT1 expression and ultimately facilitates PC cell proliferation, invasion, and metastasis by regulating aerobic glycolysis. Taken together, FOXD1 is suggested to be a potential therapeutic target for PC.

Abstract Recently, long non-coding RNAs (lncRNA) have been proven to regulate pancreatic cancer (PC) progression. We aimed to explore the pathogenesis of LINC00941 in PC regarding protein binding. By using PCR analysis, we found that LINC00941 was overexpressed in PC tissues and was higher in patients with liver metastasis than in patients without liver metastasis. In addition, high LINC00941 expression was associated with a poor prognosis. Functional experiments and mice models were respectively used to evaluate PC cell proliferation and migration in vitro and in vivo. The results suggested that LINC00941 overexpression promoted PC proliferation and metastasis. Subsequently, RNA pull-down, mass spectrometry (MS), and RNA-binding protein immunoprecipitation (RIP) were performed to identify LINC00941-interacting proteins. The results suggested that ANXA2 was the potential LINC00941-interacting protein. Nucleotides 500–1390 of LINC00941 could bind to the Annexin 1 domain of ANXA2. LINC00941-mediated malignant phenotype of PC was reversed by ANXA2 depletion. Co-immunoprecipitation (Co-IP) followed by MS was conducted to determine the potential interacting protein of LINC00941. The results illustrated that NEDD4L, an E3 ligase involved in ubiquitin-mediated protein degradation, bound to the Annexin 1 domain of ANXA2 and promoted its degradation. Mechanically, LINC00941 functioned as a decoy to bind to ANXA2 and suppressed its degradation by enclosing the domain that binds to NEDD4L. Eventually, LINC00941 upregulated ANXA2 and activated FAK/AKT signaling, increasing PC cell proliferation and metastasis. This study indicates that LINC00941 promotes PC proliferation and metastasis by binding ANXA2 and potentiating its stability, leading to the activation of FAK/AKT signaling. Our data demonstrate that LINC00941 may serve as a novel target for prognosis and therapy.

The major liver cancer subtype is hepatocellular carcinoma (HCC). Studies have indicated that a better prognosis is related to the presence of tumor-infiltrating lymphocytes (TILs) in HCC. However, the molecular pathways that drive immune cell variation in the tumor microenvironment (TME) remain poorly understood. Glycosylation (GLY)-related genes have a vital function in the pathogenesis of numerous tumors, including HCC. This study aimed to develop a GLY/TME classifier based on glycosylation-related gene scores and tumor microenvironment scores to provide a novel prognostic model to improve the prediction of clinical outcomes. The reliability of the signatures was assessed using receiver operating characteristic (ROC) and survival analyses and was verified with external datasets. Furthermore, the correlation between glycosylation-related genes and other cells in the immune environment, the immune signature of the GLY/TME classifier, and the efficacy of immunotherapy were also investigated. The GLY score low/TME score high subgroup showed a favorable prognosis and therapeutic response based on significant differences in immune-related molecules and cancer cell signaling mechanisms. We evaluated the prognostic role of the GLY/TME classifier that demonstrated overall prognostic significance for prognosis and therapeutic response before treatment, which may provide new options for creating the best possible therapeutic approaches for patients.

The mining of extra-thick coal seams features severe deformation of the stoping roadway and section coal pillars due to the large mining thickness of the coal seams and the intense movement of the overlying strata. The adjacent goaf and secondary mining disturbance in the current working face further challenge the roadway deformation control. This study explores the effect of the overlying strata structural evolution in the fully mechanized caving face of the extra-thick seam on the failure of section roadway and coal pillars. Physical analog modeling was carried out. A MatchID non-contact full-field displacement- and strain-measuring system was used to determine the evolutionary characteristics of the overlying strata breakage in the extra-thick coal seam, including the displacement variation pattern and stress/strain distribution in coal pillars. The results indicated that following the primary mining disturbance in the adjacent working face, the section roadway and coal pillars underwent initial deformation due to the primary mining-induced stress. As the mining of the current working face continued, the section roadway and coal pillars were subjected to secondary mining disturbance to the effect that the structure of the broken overlying strata gradually formed a triangular support structure. Thus, the overlying strata tilted downwards and subsided, forming a layered hanging roof structure. The additional load was then imposed on the stoping roadway and upper part of the section coal pillars. Meanwhile, the overlying strata failure caused a significant increase in the stress within the section coal pillars. Following the secondary mining disturbance, the peak stress reached a maximum of 33.62 KPa, leading to deformation and instability failure of the section roadway and coal pillars. Finally, distinctive evolutionary features of the overlying strata structure in the extra-thick and ordinary coal seams were identified, and their effect on the deformation and failure of the section roadway and coal pillars were analyzed in detail. These findings are considered instrumental in substantiating the deformation control of the stoping roadway and coal pillars in the extra-thick coal seams.

Abstract Background Studies have revealed an important role of activating transcription factor 1 (ATF1) and phosphorylated ATF1 at Ser63 in tumors. Our previous study identified Thr184 as a novel phosphorylation site of ATF1. However, the role of phosphorylated ATF1 at Thr184 (p-ATF1-T184) in tumor is unclear. This study figured out the role of p-ATF1-T184 in the metastasis of gastric cancer (GC) and in the regulation of Matrix metallopeptidase 2 (MMP2). Methods Immunohistochemical analysis (IHC) was performed to analyze the level of p-ATF1-T184 and its relationship with clinicopathological characteristics. Wound scratch test, Transwell assay were used to observe the role of p-ATF1-T184 in the invasion and metastasis of GC. The regulation of MMP2 by p-ATF1-T184 was investigated by a series of experiments including quantitative RT-PCR, western blot, gelatin zymography assay, Chromatin immunoprecipitation (ChIP), luciferase reporter assay and cycloheximide experiment. The Cancer Genome Atlas (TCGA) data were used to analyze the expression and prognostic role of ATF1 and MMP2 in GC. Mass spectrometry (MS) following co-immunoprecipitation (co-IP) assay was performed to identify potential upstream kinases that would phosphorylate ATF1 at Thr184. Results High expression level of p-ATF1-T184 was found and significantly associated with lymph node metastasis and poor survival in a GC cohort of 126 patients. P-ATF1-T184 promoted migration and invasion of gastric cancer cells. Phosphorylation of ATF1-T184 could regulate the mRNA, protein expression and extracellular activity of MMP2. P-ATF1-T184 further increased the DNA binding ability, transcription activity, and stabilized the protein expression of ATF1. Moreover, TCGA data and IHC results suggested that the mRNA level of ATF1 and MMP2, and protein level of p-ATF1-T184 and MMP2 could be prognosis markers of GC. Two protein kinase related genes, LRBA and S100A8, were identified to be correlated with the expression ATF1 in GC. Conclusion Our results indicated that p-ATF1-T184 promoted metastasis of GC by regulating MMP2.

Introduction: Objective environmental uncertainty has important impacts on entrepreneurial decision-making, but entrepreneurs’ perception of uncertainty may be a more crucial factor. This is because objective environmental uncertainty may need to be filtered through entrepreneurs’ perceptions to influence their decision-making. Therefore, exploring how entrepreneurs’ perceived environmental uncertainty (PEU) affects their corporate eco-innovation behavior has significant theoretical and practical implications.Methods: Drawing on the dynamic capability view, we utilize data from the 2016 China Private Enterprise Survey (CPES) on 2,733 small and medium-sized enterprises (SEMs) to highlight the impact of entrepreneurs’ PEU on corporate eco-innovation. We also examine the moderating effect of government intervention (government subsidies and government official visiting) on this relationship.Results: Our study reveals a positive impact of entrepreneurs’ PEU on corporate eco-innovation, confirming the critical role of dynamic capability in corporate strategic adjustment under uncertain conditions. Additionally, we find that government intervention (government subsidies and official visits) has a positive moderating effect on this relationship, with entrepreneurs’ PEU and eco-innovation being mediated by corporate dynamic capability.Discussion: The study contributes to the literature on environmental uncertainty, dynamic capabilities, and eco-innovation, and provides practical implications for SMEs in developing countries. The findings highlight the importance of subjective perceptions of environmental uncertainty over objective uncertainty. The study also demonstrates that environmental uncertainty is not inherently negative, but can be managed strategically with dynamic adjustment and government support.

Abstract Accumulating evidence has demonstrated the essential role of long noncoding RNAs (lncRNAs) in various types of human cancer, including pancreatic cancer (PC). However, the functions and regulatory mechanisms of nuclear receptor subfamily 2 group F member 1 antisense RNA 1 (NR2F1-AS1) that are responsible for its role in the malignant progression of PC cells remains to be investigated. In this study, the biological effects of NR2F1-AS1 and NR2F1 in PC were investigated by in vitro and in vivo experiments. The mechanisms of NR2F1-AS1 were monitored by bioinformatic predictive analysis and confirmatory experiments. Our results indicated that NR2F1-AS1 was overexpressed and positively correlated with poor survival in PC. Depletion of NR2F1-AS1 restrained PC cell proliferation, migration, invasion, and suppressed xenograft tumor growth and metastasis in vitro and in vivo. Mechanistic experiments suggested that NR2F1-AS1 positively regulated the neighboring NR2F1 gene, which subsequently activated AKT/mTOR signaling, resulting in the upregulation of hypoxia-inducible factor-1α (HIF-1α). Further investigations elucidated that NR2F1-AS1 expression was transcriptionally regulated by HIF-1α under hypoxia. These findings demonstrated that hypoxia-induced NR2F1-AS1 expression directly increased NR2F1 levels to promote PC cell proliferation, migration, and invasion by activating AKT/mTOR signaling. Together, these findings suggest that NR2F1-AS1 could be a prospective therapeutic target for PC.

Abstract Dysregulation of autophagy and circular RNAs (circRNAs) are involved in the pancreatic cancer (PC) progression. However, the regulatory network between circRNAs, autophagy, and PC progression remains unknown. Herein, we demonstrated that autophagy-associated circRNA circ-autophagy related 7 (circATG7) was elevated in PC tissues compared to adjacent tissues, and in PC cells treated with EBSS and hypoxia. circATG7 expression was positively associated with tumor diameter and lymph node invasion in patients with PC. circATG7 overexpression promoted PC cell proliferation, mobility, and autophagy in vitro, while circATG7 knockdown induced the opposite effects. ATG7 inhibition attenuated the effects of circATG7 on the biological functions of PC cells. CircATG7 is located in the cell cytoplasm and nucleus. Cytoplasmic circATG7 sponged miR-766-5p and decreased its expression, and increased the expression of ATG7, a target gene of miR-766-5p. Nuclear circATG7 acted as a scaffold to increase the interaction between the human antigen R protein and ATG7 mRNA and enhanced ATG mRNA stability. Furthermore, we demonstrated that circATG7 regulates PC cell proliferation and metastasis in vivo via ATG7-dependent autophagy. In conclusion, our results demonstrated that circATG7 accelerates PC progression via miR-766-5p/ATG7 and that HUR/ATG7 depends on autophagic flux. Thus, circATG7 may be a potential therapeutic target for PC.

Objective: China has undergone tremendous social changes in the last few decades. This study aimed to research the trends of the suicide rates from 2002 to 2019, and to differentiate effects attributable to age, period, and cohort by gender and residence in China. Methods: Suicide mortality data were obtained from China's Ministry of Health Vital Registration System. Joinpoint regression model was used to estimate the average annual percentage change (AAPC) of the suicide rates and ratios by gender and residence. The age-period-cohort framework was performed to analyze the underlying mechanisms for suicide mortality trends. Results: Over the observation period, the significant decrease in suicide mortality rates in China for the economic development and urbanization was observed but to different degrees across gender and regional subgroups. The male-to-female ratio of suicide rates increased year by year (AAPC: 1.9%, 95% CI: 0.2% to 3.7%) while the urban-rural ratio changed little (AAPC: 0.9%, 95% CI: −1.8% to 3.7%). The age-period-cohort analysis revealed a marked increased effect of age and overall decreased effect of both period and cohort on suicide mortality rates. However, the recent cohort has presented an inversely increasing effect. Conclusion: The suicide rate has fallen sharply in China which has undergone tremendous socioeconomic changes. The varied changes in the suicide rate of different residence-, gender-, and age-groups as well as the age, period, and cohort effect on suicide risk further indicate the relationship of development and the suicide rates may be neither static nor identical on different subgroups in a rapidly changing society.

The pipe roof is an effective means to control the surface settlement during the construction of the super-shallow buried subway station. The transverse pipe roof method can not only reduce the construction work surface, but also improve the construction efficiency by multi-stage flow construction. Based on the transfer station project of the Olympic Sports Center of Jinan Rail Transit Line 3, the ground settlement law caused by the excavation of ultra-shallow buried subway station under the action of transverse pipe roof is analyzed through field measurement. The mechanism of pipe roof controlling ground settlement and the influence of steel pipe spacing and steel pipe length on the bearing mechanism of pipe roof are analyzed by numerical simulation. The following conclusions are drawn. 1) The surface settlement curve caused by the excavation of the small pilot tunnel in the lateral direction of the station is a wavy U-shaped, and the surface settlement curve becomes a smooth U-shaped after the soil is broken. In the longitudinal direction of the station, the surface settlement is jagged, and the surface settlement above the pipe roof is less than the surface settlement between the pipe roofs. 2) After soil excavation, pipe roof can bear the load of surrounding rock and restrain the settlement of soil above, and soil arch effect is formed between pipes to restrain the relaxation of soil between pipes. With the increase of the spacing of the steel pipe, the height of the soil arch increases. After exceeding a certain spacing, the micro-soil arching effect disappears and the surface settlement increases. 3) The length and stiffness of pipe roof will affect the bearing capacity of pipe roof and there is an upper limit. When it exceeds the upper limit, increasing the length or stiffness of pipe roof has little effect on the control effect of ground settlement. The research can provide reference for shallow buried excavation station and other projects.

BackgroundOne of the most diverse tumors is pancreatic cancer (PC), which makes predicting the prognosis challenging. PC development is directly related to hypoxia, angiogenesis, and immunotherapy. It is still unclear how the three features are related.MethodsThe Genotype-Tissue Expression (GTEx) and the Cancer Genome Atlas (TCGA) database were employed to obtain sequencing data for healthy pancreatic tissues and PC tissues, respectively. According to the constructed hypoxic prognostic model (HPM) and angiogenic prognostic model (APM), 4 subtypes of PC were identified. Hypoxia and angiogenesis prognostic model (HAPM) was established based on differentially expressed genes (DEGs) between high-angiogenesis/high-hypoxia (HH) and low-angiogenesis/low-hypoxia (LL) subgroups. Base on the median risk score, PC patients were separated into high-risk and low-risk groups, and clinical traits, prognosis, percentage of immune cell infiltration, PD-1 expression, and the fraction of T-cell depletion were compared between the groups. Finally, the predictive accuracy of the tumor immune dysfunction and rejection (TIDE) and tumor inflammatory signature (TIS) models, as well as HAPM, was compared.ResultWe analyzed the mRNA sequencing data from 178 PC tissues and 171 normal pancreatic tissues to obtain 9527 DEGs. We discovered 200 genes linked with hypoxia and 36 genes involved with angiogenesis through the literature. We found the core genes related with hypoxia and angiogenesis in PC by intersecting the DEGs of the HH and LL subgroups with those of PC via WGCNA. IL-17 signaling pathway, ECM-receptor interactions, cytokine receptor interactions, etc. were all enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) results of core genes. HAPM has good predictive efficiency, according to an evaluation of KM survival curves and ROC curves. The external dataset also validated the model’s ability to anticipate outcomes. Patients in the high- and low-risk groups were compared for PD1 expression and T-cell exclusion scores, which suggested that the model might be used to forecast which PC patients might benefit from immunotherapy.ConclusionsThe probable molecular processes connecting hypoxia and angiogenesis are described in this work, and a model is developed that may be utilized to forecast the prognosis for PC patients and the benefits of immunotherapy.